DRUG INTERACTIONS (summary)-

 Folate Supplements: Avoid folate, folic acid, or folate-containing supplements within 48 hours before administration of CYTALUX.(7 

DRUG INTERACTIONS-(details)

Use of folate, folic acid, or folate-containing supplements may reduce binding of pafolacianine to folate receptors overexpressed on ovarian cancer cells and could reduce the detection of malignant lesions with CYTALUX.

Avoid administration of folate, folic acid, or folate-containing supplements within 48 hours before administration of CYTALUX)]

BRIEF SUMMARY

PAFOLACIANINE -(Nov 2021)

Indn-   To help Indentify Cance lesions

Comp-  Injection: 3.2 mg/1.6 mL (2 mg/mL) of pafolacianine in a single-dose vial.             • Recommended dosage of CYTALUX is 0.025 mg/kg administered intravenously over 60 minutes 1 hour to 9 hours prior to surgery.

ADR-  Most common adverse reactions (incidence =1%) are nausea, vomiting, abdominal pain, flushing, dyspepsia, chest discomfort, pruritus and hypersensitivity.

CI-  None. 

WARNINGS-                                                                                                                        • Infusion-Related Reactions:                                                                                         Interrupt the infusion and treat as necessary with antihistamines and/or nausea medications.

Pat Inform-

Embryo-Fetal Toxicity -

Advise females of reproductive potential of the potential risk

Folate Supplements Usage-      Inform patients that folic acid may reduce the detection of cancer tissue with the drug.. Advise the patient to stop taking folate, folic acid, or folate-containing supplements 48 hours before administration..

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U.S. FDA APPROVED DRUGS SURING 2021                                        

Serial No 47

Name of the Drug-    CYTALUX

Active Ingredient -   Pafolacianine

Pharmacological Classification- To help Indentify Cance lesions                                                                                                                                                                                                                                                                                                                         Date of Approval-          11/29/21 

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                               CYTALUX safely and effectively.                                                                                   See full prescribing information for CYTALUX. CYTALUX™ (pafolacianine) injection, for intravenous use

Initial U.S. Approval: 2021

INDICATIONS AND USAGE-

 CYTALUX is an optical imaging agent indicated in adult patients with ovarian cancer as an adjunct for intraoperative identification of malignant lesions.

ADVERSE REACTIONS-

 Most common adverse reactions (incidence =1%) are nausea, vomiting, abdominal pain, flushing, dyspepsia, chest discomfort, pruritus and hypersensitivity.

CONTRAINDICATIONS-

 None. 

WARNINGS AND PRECAUTIONS-

 • Infusion-Related Reactions:                                                                                         Interrupt the infusion and treat as necessary with antihistamines and/or nausea medications.

 • Risk of misinterpretation:                                                                                          Non-fluorescing tissue in the surgical field does not rule out the presence of tumor. Fluorescence may be seen in non-cancerous tissues.

 • Embryo-Fetal Toxicity:                                                                                             CYTALUX may cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus.

 • Risk of Pafolacianine Aggregation and Infusion Reactions:                                     Use only 5% Dextrose Injection for dilution. Do not use other diluents.

ADVERSE REACTIONS-

 Most common adverse reactions (incidence =1%) are nausea, vomiting, abdominal pain, flushing, dyspepsia, chest discomfort, pruritus and hypersensitivity.

--------DRUG INTERACTIONS ------------------------------- Folate Supplements: Avoid folate, folic acid, or folate-containing supplements within 48 hours before administration of CYTALUX.(7

DOSAGE AND ADMINISTRATION-

 • For recommended testing, evaluations, and premedications, see Full Prescribing Information.

 • Recommended dosage of CYTALUX is 0.025 mg/kg administered intravenously over 60 minutes 1 hour to 9 hours prior to surgery.

 • For preparation, management of infusion-related reactions, and imaging information see Full Prescribing Information. Should only be used by trained surgeons using FDA cleared imaging systems.

DOSAGE FORMS AND STRENGTHS-

 Injection: 3.2 mg/1.6 mL (2 mg/mL) of pafolacianine in a single-dose vial.

PATIENT COUNSELING INFORMATION -

Embryo-Fetal Toxicity -

Advise females of reproductive potential of the potential risk

Folate Supplements Usage-      Inform patients that folic acid may reduce the detection of cancer tissue with the drug.. Advise the patient to stop taking folate, folic acid, or folate-containing supplements 48 hours before administration..

Manufactured by: Grand River Aseptic Manufacturing 140 Front Ave SW Grand Rapids, MI 49506 Distributed by: Thermofisher Allentown Packaging Facility Or Patheon Logistics 100 Berkeley Dr. Swedesboro, NJ 0808

CLINICAL PHARMACOLOGY -

1. Mechanism of Action-                                                                                      CYTALUX is a fluorescent drug that targets folate receptor (FR) which may be overexpressed in ovarian cancer.

Pafolacianine binds to FR-expressing cancer cells with ~1 nM affinity, internalizes via receptor mediated endocytosis, and concentrates in FR-positive cancer tissues.

Pafolacianine absorbs light in the near-infrared (NIR) region within a range of 760 nm to 785 nm with peak absorption of 776 nm and emits fluorescence within a range of 790 nm to 815 nm with a peak emission of 796 nm.

2. Pharmacodynamics-                                                                                             Tumor to background ratios changed with different mass doses studied. High tumor to background ratio was observed with 0.025 mg/kg dose. CYTALUX exposure-response relationships and the time course of pharmacodynamic responses are unknown. Reference ID: 4886203

3. Pharmacokinetics-                                                                                                     The mean Cmax of pafolacianine was 59.1 ± 5.94 ng/mL and AUCinf was 63.6 ± 12.6 ng.hr/mL.

Distribution-                                                                                                                   The mean volume of distribution (Vz) is 17.1 ± 5.99 L, indicating distribution into tissues. Plasma protein binding of pafolacianine is 93.7%. No notable partitioning into red blood cells has been observed.

Elimination-                                                                                                                        The elimination half-life of pafolacianine is 0.44 ± 0.23 hours and mean plasma clearance is 28.6 ± 4.97 L/hr.

Metabolism-                                                                                                               Pafolacianine sodium is not metabolized by cytochrome P450 (CYP) enzymes.

Excretion-                                                                                                                       Following a single IV infusion of radiolabeled pafolacianine sodium, approximately 35% of the dose was recovered in urine (19.1%) and in feces (15.8%) after approximately 3-5 weeks.

Specific Populations-                                                                                                       No clinically significant differences in pharmacokinetics of pafolacianine were identified based on age 18 – 89 years, weight 41.6 – 133.6 kg, mild to moderate renal impairment (CLcr 30 to 89 mL/min), mild to moderate hepatic impairment (total bilirubin < 3 ULN and AST > ULN).

The effect of severe renal impairment (CLcr < 30 mL/min) and severe hepatic impairment (total bilirubin > 3 ULN and any AST value) on the pharmacokinetics of pafolacianine have not been studied.

Drug Interaction Studies -                                                                                              No clinical studies evaluating the drug interaction potential of pafolacianine have been conducted.

In Vitro Studies CYP Enzymes: Pafolacianine is not an inhibitor of CYPs 1A2, 2B6, 2C8, 2C9, 2C19 2D6, 3A4/5. UDP-glucuronosyltransferase (UGT) Enzymes: Pafolacianine is not an inhibitor of UGT1A1.

Transporter Systems: Pafolacianine is a substrate for OATP1B1, OATP1B3, and OAT1. Pafolacianine is not an inhibitor of OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1, MATE2-K, P-gp, or BCRP Reference ID: 4886203

 USE IN SPECIFIC POPULATIONS-

1 Pregnancy Risk Summary-

Based on its mechanism of action, pafolacianine may cause fetal harm when administered to a pregnant woman.

There are no available human data to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

No adverse developmental effects were observed in rats and rabbits with intravenous administration of pafolacianine during organogenesis (embryofetal development) at doses up to 158-fold (rat) and 570-fold (rabbit) the recommended human dose of 0.025 mg/kg based on AUC, otherwise 9.6 and 38.4 fold based on human equivalent dose (HED) 

The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defects, loss or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

2 Lactation Risk Summary-                                                                                    There are no data on the presence of pafolacianine in either human or animal milk, the effects on the breastfed infant, or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CYTALUX and any potential adverse effects on the breastfed infant from CYTALUX or from the underlying maternal condition.

3. Females and Males of Reproductive Potential -

CYTALUX may cause fetal harm if administered to a pregnant woman.

Pregnancy Testing-                                                                                                      Obtain a pregnancy test in females of reproductive potential and verify the absence of pregnancy prior to administration of CYTALUX [see Dosage And Administration (2.1)].

4. Pediatric Use-                                                                                                         Safety and effectiveness of CYTALUX in pediatric patients have not been established.

5. Geriatric Use-                                                                                                               Of the total number of patients in clinical studies of CYTALUX in ovarian cancer surgeries, 40% were 65 and over, while 11% were 75 and over.

No overall differences in safety, effectiveness or pharmacokinetics were observed between these patients and younger patients. Reference ID: 4886203